JPS6022716B2 - Tetrahydropyran derivatives and fungicides/insecticides - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a bactericidal/insecticide containing a novel tetrahydropyran derivative and a discussion conductor as active ingredients. The tetrahydropyran derivative of the present invention is a novel compound and is represented by the following general formula [1]. [In the formula, RI is a hydrogen atom or a lower alkyl group, R2 and R3 are both a lower alkoxy group, or one is a hydroxyl group and the other is a nitromethyl group, R4 is a hydrogen atom or a halogen atom, R5 and R6 are both a hydrogen atom, or both are An epoxy ring together with the bonded carbon atom, R7 is a lower alkoxy group when R5 and R6 are hydrogen atoms, or a hydrogen atom when R5 and R6 are epoxy rings, R8 is a hydrogen atom or a lower alkyl group, and R9 is a lower alkyl group, respectively. show. ]The above general formula [1]
Examples of the lower alkyl group include a methyl group,
Ethyl group, propyl group, isopropyl group, butyl group, t
Examples include en-butyl group, bentyl group, and hexyl group. Examples of the lower alkoxy group include methoxy group, ethoxy group, propoxy group, isopropoxy group, putoxy group,
Examples include rt-butoxy group, benzyloxy group, hexyloxy group and the like. Conventionally, the compound closest to the tetrahydropyran derivative represented by the above general formula [1] of the present invention is the following general formula:

A compound represented by [0] is known (US Pat. No. 4,059,595). [In the formula, AI is a hydrogen atom, an alkyl group having 1 to 10 carbon atoms,
and A2 represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, or an acyl group having 1 to 10 carbon atoms] However, the compound of the present invention is different from the above-mentioned known compound in that it contains at least one type of compound bonded on its tetrahydropyran ring. Based on the difference in substituents, as will be described later, it has the feature of exhibiting an antibacterial effect and an insecticidal effect that cannot be predicted from the above-mentioned known compounds. Representative compounds included in the tetrahydropyran derivative of the present invention represented by the above general formula [1] are as follows. 04-chloro-3,4-epoxy-2-methoxy-5-
Nitromethyl-5-hydroxy-6-isopropyl-tetrahydropyran 04-fluoro-3,4-epoxy 2,6-diethoxy-5 nitromethyl-5-hydroxy-tetrahydropyran o2-methoxy-3,4-epoxy 3,4-epoxy 5-nitromethyl-5- Hydroxy-tetrahydropyran o-6 Ethyl-2-methoxy-3,4-epoxy 5-nitromethyl-5-hydroxy-tetrahydropyran 04-Fluoro-6-ethyl-2-ethoxy 3,4-epoxy-5 nitromethyl-5-hydroxy-tetrahydropyran 04-chloro-
2-methoxy 2,6-dimethyl-3,4-epoxy
5-nitromethyl-5-hydroxy-tetrahydropyran o4-chloro3,4-epoxy2-methoxy2
-Methyl-5,5-diethoxytetrahydropyran 0
4-fluoro-3,4-epoxy 2,5,5-trimethoxytetrahydropyran o4-chloro-3,4-epoxy-2,6,5,5-tetramethoxytetrahydropyran o4-promo-3,4-epoxy-2-methoxy 5,5-dibutoxy-6-ethyl-tetrahydropyran o4-chloro3,4-epoxy-2-methoxy-2-methyl-5,5-diethoxytetrahydropyran o4-bromo3,4-epoxy-2,5,5-trimethoxy Cetetrahydropyran o4-chloro3,4-epoxy-6-ethyl-2,5,5-trimethoxytetrahydropyran 02,3,5,5-tetramethoxy-4
-bromotetrahydropyran 02,3,5,5-tetraptoxy 4-furomotetrahydropyran 02,3
-5,5-tetraethoxy-4-chlorotetrahydropyran The tetrahydropyran derivative of the present invention can be produced, for example, by the methods shown in Reaction Schemes 1-1 and 2 below. <Reaction Scheme-1> [In each of the above formulas, R1, R8 and R9 are the same as above. RI0 represents a lower alkyl group and X represents a halogen atom.
] In the above reaction scheme 1, the compound represented by the general formula [blood] is reacted with an alcohol represented by the general formula RI℃day in the presence of a halogenating agent and in the absence of a solvent, to form a compound represented by the general formula [blood]. Compounds of the present invention represented by [1] wherein R2, R3 and R7 are lower alkoxy groups, R4 is a halogen atom, and R5 and R6 are hydrogen atoms [
W] can be manufactured. Examples of the halogenating agent used in the above include fluorine, chlorine, bromine, iodine, etc., and the amount used is equal to or more, preferably equimolar to 1.2 times the mole of the compound represented by the general formula [m]. It is better to Further, the alcohol represented by the general formula RI°C is usually used in a large excess amount relative to the compound represented by the general formula [m]. The above reaction is carried out at -30oo to room temperature, preferably from 0 to 10
It is carried out for 1 to 3 hours at ℃. <Reaction Scheme-2> [In each of the above formulas, R1, R4, R5, R8, R7, R8 and R9 are the same as above. RII represents a hydrogen atom or a lower alkyl group, and R12 represents a lower alkyl group. ] In the above reaction scheme-2,
The starting compound is a compound represented by the general formula [V],
By reacting a nitroalkane represented by the general formula RIICH2NQ in the presence of a basic compound, a compound [W] in which R2 is a hydroxyl group and R3 is a 1-nitromethyl group in the compound represented by the general formula [1] of the present invention can be obtained. You can earn it. The above reaction is carried out in the presence of the above-mentioned basic compound in a suitable solvent of the above-mentioned lower alcohols, ethers, or halogenated hydrocarbons. The nitroalkane used in the reaction usually has the general formula [V]
The amount of the basic compound is usually catalytic, preferably 0.01 to 0.0. It is preferable to set it to 0 needle sound molar. The reaction is generally completed at -3 to 0 to room temperature, preferably from 0 to 20, for 2 to 6 hours. Further, in the above reaction scheme-2, the compound represented by the general formula [V] is reacted with the compound represented by the general formula CH(OR12)3 using an acid catalyst, thereby converting the general formula [V] of the present invention into a compound represented by the general formula [V]. A compound represented by [1] in which R2 and R3 are lower alkoxy groups [skin]
can be obtained. This reaction is carried out in the various solvents mentioned above. Examples of the acid catalyst used include organic sulfonic acids such as p-toluenesulfonic acid and ethanesulfonic acid, Lewis acids such as zinc chloride, calcium chloride, and magnesium chloride. The amount of the compound represented by the general formula CH (OR position) 3 to be used is usually 0.5 x 1 molar, preferably 0.6 to 2 times the molar amount of the compound represented by the general formula [V]. The acid catalyst may be used in a usual catalytic amount, preferably 0.05 to 0.00% relative to the compound represented by the general formula [V]. It can be used as an antiphonal mole. The reaction is generally completed in 1 to 6 hours at 30 to 150°C, preferably 50 to 8 picoC. The starting compound, the compound represented by the general formula [V], is a known compound or can be produced, for example, by the following reaction scheme-3. <Reaction Scheme-3> [In each of the above formulas, R1, R4, R8 and R9 are the same as above. R13 represents a lower alkyl group. ]Above reaction scheme-3
In this method, by reacting an epoxidizing agent with a known bilane derivative represented by general formula [W], R5 and R6 in the compound represented by general formula [V], together with the carbon atoms to which they are bonded, form epoxy moieties and A compound [K] in which R7 represents a hydrogen atom can be produced. The above reaction is carried out in a suitable solvent in the presence of a basic compound. Examples of solvents include water, ethers such as diethyl ether, tetrahydrofuran, and dioxane, lower alcohols such as methanol, ethanol, and propanol, lower fatty acids such as acetic acid and propionic acid, and halogenated carbons such as methylene chloride, chloroform, and carbon tetrachloride. Qin etc. can be used. As the basic compound, for example, inorganic basic compounds such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, and basic ion exchange resins can be used. Further, as the epoxidizing agent, for example, peracetic acid, pertrifluoroacetic acid, benzoic acid, m-chloroperbenzoic acid, hydrogen peroxide, etc. can be used. The groups used for the epoxidizing agent and the basic compound are:
Usually, the amount is 0.5 to 3 times the mole of the compound of general formula [W], preferably the same mole to 1.2 times the mole, and 0.1 times the mole to the same mole, preferably 0.2 to 0.5 times the mole. It is better.
The reaction is carried out at a temperature of -30 to 4 psi, preferably -20 to 2 psi, for 2 to 6 hours. In addition, the above reaction scheme-3
In this method, by reacting the compound represented by the general formula [W] of Kosanku with an alcohol represented by the general formula RI℃day in the presence of a basic compound, the general formula [V
] In the compound represented by R5 and R6 are hydrogen atoms and R
A compound [X] in which 7 represents a lower alkoxy group can be produced. This reaction is usually carried out in the absence of a solvent at a temperature of -3 to 0 to 0, preferably at room temperature.
It takes 30 minutes to 3 hours at a temperature of /2 and 0. The basic compounds used in the above include potassium hydroxide, sodium hydroxide, sodium methylate,
Examples include alkali metal alcoholates such as potassium methylate, sodium ethylate, and sodium propylate. The amount of the basic compound and the alcohol represented by the general formula RI°C days to be used is a usual catalytic amount, preferably 0.01 to 0.05 tomole, and a large excess amount, respectively, relative to the compound of the general formula [W]. And it is sufficient. In this way, the compound represented by the general formula [1] of the present invention can be obtained. The desired compound produced in each step can be easily purified in a single unit by conventional separation means such as solvent extraction, distillation, silica gel column chromatography, etc.
The tetrahydropyran derivative represented by the general formula [1] of the present invention has a remarkable bactericidal effect against various bacteria and fungi, and also has a remarkable bactericidal effect against various pests such as agricultural and horticultural pests,
It also has a strong insecticidal effect against forest pests, sanitary pests, etc., and various mites, and therefore is useful as a sterilizer and insecticide for bacteria, fungi, and pests, especially against plant damage caused by bacteria, etc. It is useful as a disinfectant and insecticide for agriculture and horticulture. In addition, the tetrahydropyran derivative represented by the general formula [1] of the present invention can be blended into a paint in an appropriate form or dissolved in various organic solvents such as acetone, methanol, ethanol, chloroform, hexane, ether, etc. do,
It can prevent contamination caused by the above-mentioned bacteria, mold, etc., and damage to equipment, equipment, etc., and can also be applied to various industrial water such as cooling water and papermaking water, resulting in the growth of algae caused by bacteria and mold. can also be prevented or suppressed. Therefore, the present invention also includes bactericides and insecticides containing the tetrahydropyran derivative represented by the above general formula [1] as an active ingredient. When using the bactericidal/insecticide of the present invention, in the same way as the three commonly used bactericidal/insecticides, appropriate solid carriers, liquid carriers, suspending agents, spreading agents, etc. are added as necessary. The active ingredient compound represented by the general formula [1] can be prepared into any form such as granules, powders, dispersants, wettable powders, tablets, oils, atomizers, and atomizers. The carriers used include clay, kaolin, bentonite, talc, acid clay, celiac earth, calcium carbonate, nitrocellulose, starch, gum arabic, carbon dioxide gas,
Examples include freon, water, benzene, kerosene, alcohol, acetone, xylene, methylnaphthalene, cyclohexanone, and animal and plant fatty acid esters. Suspending agents, spreading agents, etc. include common surfactants such as soaps, sulfate esters of higher alcohols, alkyl sulfonates,
Examples include quaternary ammonium salts and polyalkylene oxides. The amount of the compound represented by the general formula [1] in the drug of the present invention prepared as described above can be appropriately determined depending on the form of use and the like. For example, in order to form a dispersant or a wettable powder, 0.1 to 9
The content is preferably in the range of 0% by weight, and in the form of powders, oils, etc., the content is preferably in the range of about 0.1 to 10% by weight. When using the bactericidal/insecticide of the present invention, it can be applied by spraying, misting, coating, etc. to the area where the bactericidal/insecticide effect is required in the same way as known bactericidal/insecticides, and the amount of application is It can be determined as appropriate depending on the desired effect. For example, when using the drug of the present invention for agricultural and horticultural purposes, usually 1
The amount of active ingredient per hectare may be 0.1 to 10k9, preferably 0.1 to 5k9, and of course this can be increased or decreased as appropriate depending on the plants and the degree of damage to them. It can also be used in combination with, for example, other fungicides, insecticides or herbicides, fertilizer substances, soil conditioners, etc. In order to further explain the present invention, the results of an antibacterial test and a rodent test are listed below. 1. The following compounds 1 and 2 of the present invention and compounds a and b for comparison are used as antibacterial test compounds. <Mysterious compound> Compound 1...2,3,5,5-tetramethoxy-4-bromotetrahydropyran compound 2...
...3.4-epoxy-2-methoxy-5-hydroxy-5-nitromethyl-6-ethyl-tetrahydropyran compound 3...4-chloro3.4-epoxy-2-methoxy-2-methyl-5.5 -Diethoxytetrahydropyran compound a (comparison)...
... 3,4-epoxy-2-methoxy 5-oxotetrahydropyran compound b (comparison) ...
・3,4-epoxy 2-ethoxy-6-methyl-5-
Make a 2% solution of each test compound such as oxotetrahydropyran in acetone, dilute it with water to the specified concentration, place solution 1 of each concentration in a petri dish, and add potato dextrose of 9. Mixed with agar toji (PDA toji),
Agar plates with various concentrations of each of the above-mentioned donor compounds are prepared. Punch out the tip of the mycobacterium of the mystery bacterium, which has been pre-wilted in PDA medium, using a cork pole with a diameter of IQ side to create a disc of the bacterium, and place this disc with the bacterium side down on each of the agar plates prepared above. Silence above. The presence or absence of fungal growth was visually observed after 2 days, and the lowest inhibitory concentration (leg) for completely inhibiting fungal growth is shown for each mystery bacterium in Table 1 below. The mystery bacteria in each table are as follows. <Test bacteria> A...... Rice white hollyhock blight fungus 8... Cucumber spot bacterium C... Vegetable soft rot fungus D... ... Rice mochi fungus E... Rice, Sesame, Aoi blight fungus F... Eggplant sclerotium G... Melon vine blight fungus Day... ...Tomato ringworm fungus Table 1 Table 0 Insecticidal test 'a- Dissolve the test compound in acetone to make a 2% solution,
This is diluted with deionized water to a predetermined concentration (2Q4). In the test, 4th instar larvae of A. japonica were placed in a petri dish 9 melons in diameter and 7 inches in height, covered with a glass lid, and placed in 200 piles of the chemical solution.
This is done by transferring 0 individuals and investigating whether they are alive or dead at the time of emergence.
Results are expressed as mortality rate (%). Test compound Mortality rate (%) Compound 1
70 compounds 3
50〃 a (comparison) 5
'b' A furnace paper on which 0.5' of a 2% acetone solution of the test compound was dropped was transferred to a petri dish, and 20 adult female house flies on the 3rd to 4th day of emergence were used. Investigate
The mortality rate (%) was determined. Compound provided Mortality rate (%) Compound 1
55. a (comparison)
5 Hereinafter, in order to explain the present invention in more detail, production examples of the compounds of the present invention will be given as Examples. Example 1 4-chloro-3,4-epoxy-2-methoxy-6-isopropyl-5-oxotetrahydropyran Shoyu and 7.3 moles of nitromethane were added to 150 methanol and heated to 0 to 10 °C under Nawa Azusa. Drop onto 2M-KOH/C horse OHIO for 1 hour. After dropping, the mixture was kept for 2 hours at 10~lyo, neutralized with 10% tartaric acid aqueous solution, methanol was removed under reduced pressure, and the residue was extracted with methylene chloride. was isolated and purified by silica gel column chromatography to obtain 4-chloro-3,4-epoxy-2 as a yellow oil.
-methoxy-5-nitromethyl-5-hydroxy-6-
25.1 tons of isopropyl-tetrahydropyran are obtained.
m analysis result (fertility) 344 ratio Ne-1 (OH) 159 pieces 1 spot 2-1 (N02) Elemental analysis value (C, rainbow, as 606 NCI) Calculated value (%
) C42. Unehi 573N4.97 Actual measurement value (%) C4
2.81 days 5. Group N5 female Compounds of Examples 2 and 3 below are obtained in the same manner as in Example 1 above. Example 2 2-methoxy-3,4-epoxy-5 nitromethyl-5-hydroxy-tetrahydropyran Properties Pale yellow oil Boiling point Total ~86℃/0.01 field Hg elemental analysis value (C7 days, as .QN) Calculated value (%) C40. Spot day 5.40N6 spot actual measurement value (%
) C40.75 days 531N674 Example 36-ethyl-2-methoxy-3,4-epoxy-5nitromethyl-5-hydroxy-tetrahydropyran Properties Pale yellow oil m Analysis results (female at) I4 ratio Nu-1 (OH) 15601 spots 2-1 (NQ) Elemental analysis value (as C9th, 5QN) Calculated value (%) C4635HO crab NOOI actual value (%)
C4648 day 6.57N612 Example 44-chloro-3,4-epoxy-2-methoxy-2-methyl-5-oxotetrahydropyran 19.2 nights, p-toluenesulfonic acid 1.0 nights and ethyl orthoformate 12.0 nights was added to 200 ml of benzene, refluxed for 2 hours, and then cooled. The reaction solution was washed with an aqueous sodium bicarbonate solution and then with brine, dried, and the solvent was removed under reduced pressure. The residue was isolated and purified by silica gel column chromatography to obtain a yellow oily 4-
22.6 hours of chloro-3,4-epoxy-2-methoxy-2-methyl-5,5-diethoxytetrahydropyran are obtained. NMR analysis result (CDC13) 1.6Q- (S, group, C ratio) 35 females (S, group, dish 3) Elemental analysis value (C, day, 905CI) Calculated value (%
) C49. Departure 7.18 Actual value (%) C49.71
Day 7.29 Example 5 2-Methoxy5-oxo 5,6-dihydro 2H-
Add 12.8 parts of pyran to 100 parts of methanol, and dropwise add 30 parts of a methanol solution of 16 parts of bromine at 0 to 5 DEG C. over 1 hour. After the dropwise addition, malting was continued for 1 hour at the same temperature, and then 11 hours of triethylamine was added dropwise, and the solvent was distilled off under reduced pressure. The residue is extracted with methylene chloride, washed with brine and dried, and the solvent is removed under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain yellow oily 2.3.
5,5-tetramethoxy-4-furomotetrahydropyran 181 is obtained. NMR analysis results (CDC13) 3.2 perfect example (S, but, C ratio 0) 3.3 morning blood (S, but, C ratio is 0) 34 foggy (S, thin, C ratio is 0) Elemental analysis value ( C9 days, 7QBr) Calculated value (%) CaB18 days 6.05 Actual value (%) C3801 days 6.02 Examples of formulations are given below. Formulation Example 1 The above two materials are mixed and polished to obtain a powder. Formulation Example 2 The above components are mixed to obtain a wettable powder. Formulation Example 3 4-Chloro-3,4-epoxy 2-methoxy-5 nitromethyl-5-hydroxy-6-isoprop The above components are mixed and polished, and then granulated using a granulator to obtain granules.

Claims (1)

[Claims] 1 General formula▲ Numerical formula, chemical formula, table, etc.▼ [In the formula, R^1 is a hydrogen atom or a lower alkyl group, R^2 and R^3 are both a lower alkoxy group, or one is a hydroxyl group The other is a 1-nitromethyl group, R^4 is a hydrogen atom or a halogen atom, R^5 and R^6 are both a hydrogen atom or an epoxy ring together with the carbon atom to which they are bonded, R^7 is RR^5 and R^6 is a hydrogen atom, lower alkoxy group or R^5
and when R^6 is an epoxy ring, it is a hydrogen atom, R^8 is a hydrogen atom or a lower alkyl group, and R^9 is a lower alkyl group. ] A tetrahydropyran derivative represented by 2 General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [In the formula, R^1 is a hydrogen atom or a lower alkyl group, R^2 and R^3 are a lower alkoxy group, or one is a hydroxyl group and the other is a 1-nitromethyl group, R^4 is a hydrogen atom or a halogen atom, R^5 and R^6 are both a hydrogen atom or an epoxy ring together with the carbon atom to which they are bonded, and R^7 is R^5 and R^
When 6 is a hydrogen atom, lower alkoxy group or R^5 and R
When ^6 is an epoxy ring, it is a hydrogen atom, R^8 is a hydrogen atom or a lower alkyl group, and R^9 is a lower alkyl group. ] A bactericidal/insecticide containing a tetrahydropyran derivative represented by the following as an active ingredient.